About 1/3rd of the 40 million people living with Human Immunodeficiency Virus (HIV) worldwide are co-infected with Mycobacterium tuberculosis. Treatment of tuberculosis (TB) is of particular concern in HIV-infected individuals, because the pharmacokinetic (PK) interactions between antiretrovirals (ARV) and rifamycins are not well characterized. Patients with HIV and TB who are treated with non-rifamycin-containing regimens have clearly inferior outcomes. The Department of Health and Human Services recommends the use of rifampin (RMP) with a regimen consisting of one of the non nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) or nevirapine (NVP) plus 2 nucleoside reverse transcriptase inhibitors (NRTI), or ritonavir and/or saquinavir and 2NRTI, or a triple NRTI regimen. There is a controversy about the need to adjust the dose of EFV or NVP in this setting. The primary aims of this research proposal are to evaluate the drug exposure and virological responses to two doses of EFV, 600mg or 800mg/day or two doses of NVP, 200 or 300 mg twice daily, combined with RMP, 600mg/day, early and late during TB therapy in patients with HIV infection. The longitudinal design will evaluate the possibility of a time-dependent change in EFV or NVP exposure that may occur as the patient's overall condition improves. A secondary aim is to determine the tolerability of both proposed treatment regimens. This study will provide information as to the necessity of adjusting the dose of EFV or NVP to maintain sufficient drug exposure when either is used concurrently with RMP, thus avoiding HIV drug resistance and treatment failure in that population. This study will be carried out in collaboration with an international site located in Salvador, Bahia, Brazil. There is a high prevalence and incidence of TB and HIV infection in that region. We will conduct an open label, randomized clinical trial in approximately 200 HIV infected, ARV naive subjects who have a simultaneous clinical and/or laboratory diagnosis of TB. These subjects will start antituberculous treatment (RMP + isoniazid + pyrazinamide) and 4 weeks later will be randomized between two treatment arms containing different doses of EFV or NVP plus 2 NRTI. After the introduction of EFV or NVP, PK studies to assess the area under the concentration time curve for EFV and NVP will be performed at weeks 2 and 36. Virological efficacy of the different doses of EFV and NVP will be assessed. The incidence of central nervous system adverse events (neuropsychological/mood), hepatotoxicity, skin reactions and immunologic and virological signs of treatment failure will be monitored and compared between arms. [unreadable] [unreadable]